Imaging of the vulnerable carotid plaque: biological targeting of inflammation in atherosclerosis using iron oxide particles and MRI.

Objectives Identification of those patients with high-risk asymptomatic carotid plaques remains an elusive but essential step in stroke prevention. Inflammation is a key process in plaque destabilization and the propensity of atherosclerotic lesions to cause clinical sequelae. There is currently no clinical imaging technique available to assess the degree of inflammation associated with plaques. This study aims at visualizing and characterizing atherosclerosis using antibody-conjugated superparamagnetic iron oxide (SPIO) particles as an MRI probe to assess inflammation in human atherosclerotic plaques. Methods Atherosclerotic plaques were collected from 20 consecutive patients ( n  = 10 from symptomatic patients, n  = 10 from asymptomatic patients) undergoing carotid endarterectomy (CEA) for extracranial high-grade internal carotid artery (ICA) stenosis (>70% luminal narrowing). Inflammatory markers on human atherosclerotic plaques were detected and characterized by ex vivo magnetic resonance imaging (MRI) using anti-VCAM-1 antibody and anti-E-selectin antibody-conjugated SPIO with confirmatory immunohistochemistry. Results Inflammation associated with human ex vivo atherosclerotic plaques could be imaged using dual antibody-conjugated SPIO by MRI. Symptomatic plaques could be distinguished from asymptomatic ones by the degree of inflammation, and the MR contrast effect was significantly correlated with the degree of plaque inflammation ( r  = .64, p Conclusions These functional molecular MRI probes constitute a novel imaging tool for ex vivo characterization of atherosclerosis at a molecular level. Further development and translation into the clinical arena will facilitate more accurate risk stratification in carotid artery disease in the future.